On January 12, 2022 Lantern Pharma (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported it has expanded its collaboration agreement with the Developmental Therapeutics Branch (DTB) of the National Cancer Institute (NCI) of the National Institutes of Health (Press release, Lantern Pharma, JAN 12, 2022, View Source [SID1234598628]). The expansion of this collaboration comes after identifying several gene signatures that predict a potential response of a patient’s tumor to Lantern’s drug candidates, LP-184 and LP-284. LP-184 is being pursued as a new therapy across a range of genetically defined solid tumors, including pancreatic cancer and GBM (Glioblastoma Multiforme). LP-184 was presented as a novel agent effective in GBM at SNO (Society of Neuro-Oncology) in November of 2021. LP-284 is being developed as a new therapy for certain leukemias and lymphomas as presented for the first time in December at the 2021 ASH (Free ASH Whitepaper) Annual Meeting.
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"This expanded collaboration with the NCI is further evidence of the power of combining multiomic data with our A.I. platform, RADR, to accelerate the cost-effective and biomarker guided development of targeted oncology therapies," stated Dr. Kishor Bhatia, Chief Scientific Officer of Lantern Pharma. "We look forward to publishing our first in human Phase 1 results in peer-reviewed publications and bringing our potential cancer therapies to patients through the power of A.I. and data."
The first phase of the collaboration with the DTB Genomics and Pharmacology Facility at NCI successfully identified biomarker correlations from multiomic NCI datasets that will be used to guide the accelerated development of Lantern’s drug candidates. The biomarker correlations are being used for LP-184 and LP-284 to: 1) uncover insights into the mechanisms of action 2) develop a signature predicting the response of a tumor, 3) prioritize the sub-types of cancer most likely to respond in a manner that would improve the current standard of care and, 4) generate data and models to guide the selection of other approved drugs that can be used in combination with LP-184 and LP-284.
The second phase of the collaboration will leverage the data and functionality provided by NCI’s complementary CellMiner and CellMinerCDB platforms to examine additional multiomic data for more accurate and powerful drug response correlation. This phase will also include data from Project Achilles at the Broad Institute, which is integrated into the CellMiner platform, to compare how Lantern’s complete drug candidate portfolio compares with other anti-cancer drugs under specific genetic and molecular conditions. The additional data and expanded analytic toolbox, including epigenetic, proteomic and microRNA data types, will enable Lantern to further refine multiomic signatures predictive of drug efficacy into a curated list of candidate biomarkers. These biomarkers can be utilized in gene editing and CRISPR technology studies to derisk development decisions and validate additional therapeutic strategies. Lantern will be using this rigorous approach to guide future development initiatives for itself and for potential development and commercial partners.
"The data generated from this collaboration will further advance and scale the capabilities of the RADR A.I. platform for potentially breakthrough drug discovery and development," stated Panna Sharma, CEO of Lantern Pharma. "The new data will drive insights and drug-candidate innovations and also lead to additional biopharma collaboration and partnership opportunities."
Lantern and the NCI expect to publish the research results of this collaboration in peer-reviewed journals. Early data indicates the uniqueness of the correlation of LP-184 with PTGR1 expression compared to other therapeutic agents in the database. Gene correlation comparisons between LP-184 and other DNA targeting agents support LP-184’s potential as a more effective drug candidate in tumors that show resistance to other DNA targeting agents, including synthetic lethal agents.
The data types in the NCI datasets included, DNA mutation, mRNA/ miRNA expression, DNA methylation, DNA copy number and protein data. This data was then used to characterize Lantern’s pipeline of drug candidate and their bioactivity profiles through NCI’s CellMiner platform. These multiomic analyses have provided deeper insights into the mechanism of action, efficacy profile and optimal cancer indications for Lantern’s pipeline of drug candidates in preclinical and clinical development. This analysis has aided in the accelerated development of the DNA damaging agents LP-184 and LP-284. Initial work helped identify several hundred genes whose transcript levels significantly correlated both positively and negatively with pan-cancer sensitivity to LP-184. Additional correlations were found for LP-284 that aided in targeting subsets of blood cancer indications. The expression of PTGR1, which was among the strongest correlations, reinforced a critical component underlying LP-184 sensitivity and was further validated in vitro and in vivo across several tumors.
Several negatively correlated genes confirmed the enhanced LP-184 sensitivity in tumors that harbor compromised DNA repair pathways. For example, the negative correlation of LP-184 sensitivity with methylation of MGMT substantiate the potential for higher sensitivity of LP-184’s efficacy in MGMT methylated tumors – an important therapeutic refractory feature in glioblastomas. The availability of multiomic data such as methylation data and protein data continue to support areas of applicability of such correlations.
LP-184 is being developed for multiple targeted oncology indications. Lantern Pharma intends to further advancing LP-184 as a new, potent treatment option in genetically defined subsets of patient populations in areas of high unmet clinical need, including pancreatic cancers, GBM, and other cancers that are DNA damage repair deficient. The U.S. Food and Drug Administration (FDA) granted LP-184 Orphan Drug Designation for the treatment of pancreatic cancer and GBM and other malignant gliomas in August 2021. LP-284 is expected to be developed for multiple hematological indications, including several rare sub-types of leukemia and lymphoma.